C9 and amyotrophic lateral sclerosis: Although the mild phenotypes in a homozygous C9ORF72 mutation case and the lack of C9ORF72 coding mutations suggest that wild-type protein loss-of-function is unlikely the primary cause of C9-ALS/FTD (Fratta et al., 2013; Harms et al., 2013), loss-of-function of the wild type protein is still a possible mechanism that contribute to the disease pathogenesis.